Alkoxyacridines



Patented May 28, 1929 'LoUIs IBENDA, or .mamxun,

scmnnr, or rncnnnnnm,

SIGNORS TO WINTHROP CHEMICAL COMPANY,

IPOBATION OF NEW YORK.

No Drawing. Application .flled April 20, 1923, Serial No. 634,895, and in Germany We have found that by the action of alkyl ating agents hydroxyacridines, as for ina stance 3.6-dihydroxyacridine-Benda, Be

richte 45,1704 (1912) 2.7 -dimethyl-3,6-dihydroxyacridine (German Patent 121686 Kl. 22 and others, may be converted into O alkyl ethers, without at the same time alkylating the nitrogen nucleus. The bases of the new compounds correspond to the formula R0 OK R means an alkyl radical.

Owing to their non-toxicity and high inhibitory power in respect of bacteria the new products are adapted for the prevention and cure of a great variet of infections. The dimethylether in experiments on animals has proved nearly non-toxic, still arrests for instance the growth of-diphtheria bacilli, and streptococci, even if applied in a highly diluted form, whereas 3.6-d1hydroxyacridine remains practically ineflective, even if administered in a highly concentrated form. Also the O-monoalkylethers of the dihydroxyacridines, formin in addition to the dialkylethers, are valua curatives.

Example I .3.6-dimethoxyacridine.

011.0 -oom N 211 gr. 3.6-dihydroxyacridine are dissolved in 2000 cc. water with the addition of 80 gr. 256 gr. dimethylsiilphate are free base is roduced in the usual manner.

The alka me mother liquor contains mon- I .&

NEAR IRANKFOR'J!-ON-'.l3IHllil-IH[AIIT1\T, NEAR FRANKFOBT-ON-THE-MAIN, GERMANY, AS-

anxoxyaoaminns.

of 3.6-d1hydroxyacridine which I le disinfectants and ly colored needles. From the hydrochloride the AN D WERNER INC., 01 NEW YORK, N; Y., A COR- Hay 24, 1922.

omethylether of the 3.6-dihydroxyacridine. It s produced from the solution by exact neutrahzing with acetic acid.

3.6-dimethoxyacridine C H NO It crystalizes from ether in fine, slightly yellowish needles, or stout, light'yellow crystals of a melting point (uncorr.) of 138139 C. It is readily soluble in warm 'ether, alcohol, methyl alcohol, benzene and acetone, sparingly soluble in hot water, and insoluble in dilute alkalies and carbonates of alkalies. In concentrated sulphuric acid the solution is yellow and strongly greenish fluorescent. In glacial acetic acid and in hot, dilute mineral acids dimethoxyacridine dissolves easily with a ellow color and green fluorescence, and on ding an excess of dilute mineral acid, the respective salts crystalize in theform of yellow needles. 1

Ewample l I .3.6-diethoxyacridine.

' CaHsO .OCaHI 106 gr. 3.6 dihydroxyacridine are dissolved hot with 2 litres water and 100 cc. caustic soda solution 38 B. The solution is filtered and While hot, 200 gr. diethylsulphate are graduallyadded, stirring well. Heating in the water bath is continued until the solution reacts nearly neutral, 35 gr. caustic soda solution added and after complete reaction the 3.6-diethox acridine is filtered ofl'.. By careful neutra izing the alkaline mother liquor with acetic acid, slight quantities of monoethylether are obtained.

3.6-diethoxyacridine crystallizes from ether in fine, yellow needles of 142-143 0., melting point (uncorn). The solubility of the base corresponds with that of the dimeth oxyacridine. The salts are soluble in water than those of the base named; The hydrochloride crystallizes in reddish needles of bluish shining surface.

I'a2ample IlI.3.6-bishydroxy ethoxy acr1 me.

aoornomo oomcmori mixed with 84 gr. 3.6-dihydroxyacridine are cc. caustic soda solution 40 far less readily- After opening, the contents are cooled down water and 150 cc. alcohol, adding 80 gr. ethylenechlorhydrin, and heating the m1x ture for 3 hours at 150 C. in an autoclave.

to 0 C., the precipitated 3.6-bishydroxy ethoxy acridine stirred for 5 hours in dilute caustic soda solution, and after sucking ofi dissolved with dilute hydrochloric acid, procipitated once more with soda solution, and

finally recrystallized from alcohol. The base thus obtained is representedby slightly reddish-yellow vcrystals of melting point 200C.

It is insoluble in a carbonate of soda solution, also in cold soda solution, sparingly soluble in hot soda solution, precipitating in. this solution on cooling down; in hot water' it is' difiicultly soluble and practically insoluble in cold, dissolving in concentrated sulphuric acid with a fal 0w color and slightly greenfluorescence.

It mayalso be produced without pressure and alcohol byfheating the mixture for 36 hours in the 011 bath to 150-160 C.

Havin ow particularly described and ascertaine t e matter of our said invention and in what manner the same is to be performed, we declare that what we claim is:

1; A roce'ss for the production of dialkoxyacrldines by heating 3.6-dihydroxyacridines in the presence of acid-binding substances with alkylating agents.

- acridines corresponding to the formula:

no (l non in which formula It means an alkyl radical and X means an anion, being yellow water soluble crystalline compounds.- 7

4. As .a new substance the hydrochloride of 3.6-dimethoxyacridine, corresponding probably to the formula]:

k cn

cH.o O\ I) oon= K crystallizing in light yellow needles, soluble in hot water, scarcely soluble in cold water.

In witness whereof we have hereunto signed our names this 29th day of March,

LOUIS BENDA. WERNER SCHMIDT. 

